Mathematics in Kerala, during the times of Madhava of Sangamagrama, majorly flourished in the Misiris region of Thrikkandiyur, Thirur, Alathiyur and Thirunavaya in the Malabar region of Kerala. Commemorating the rich heritage of Mathematics in the region, Kerala School of Mathematics was hence chosen to be set up in the scenic mountains of the Western Ghats in the city of Kozhikode.
The nascent plan to set up Kerala School of Mathematics started forming shape in around 2004. The then DAE chairman Anil Kakodkar and the then executive vice president of KSCSTE, M. S. Valiathan were instrumental in setting up the institute with the guidance of M. S. Raghunathan, Rajeeva Karandikar and Alladi Sitaram. The foundation stone of KSoM was laid by the then Chief Minister A.K. Antony in 2004. The institute was later inaugurated in 2008 by the then Chief Minister V. S. Achuthanandan and finally set up in 2009 with Parameswaran A. J. as the founding director.